Localized tyrosine or tetrahydrobiopterin supplementation corrects the age-related decline in cutaneous vasoconstriction

The attenuated reflex vasoconstriction in aged skin may be partly mediated by oxidant-induced reduction in functional substrate and cofactor availability for noradrenaline biosynthesis. We hypothesized that localized supplementation of tyrosine and tetrahydrobiopterin (BH₄) in aged human skin could augment reflex- (whole-body cooling) and pharmacologically (tyramine, which displaces noradrenaline from axon terminals) induced vasoconstriction. Four microdialysis fibres were placed in the forearm skin of 10 young and 10 older subjects for infusion of (1) Ringer solution (control), (2) 0.5 mm l-tyrosine, (3) 5 mm BH₄, and (4) BH₄+l-tyrosine. Cutaneous vascular conductance (CVC) was calculated (laser Doppler flux/mean arterial pressure) and normalized to baseline (%ΔCVC_base). Vasoconstriction was attenuated at the control site in the older subjects during both whole-body cooling (young: -39 ± 3, older: -17 ± 3%ΔCVC_base; P < 0.01) and tyramine infusion (young: -41 ± 3, older: -21 ± 4%ΔCVC_base; P < 0.01). BH₄ (cold, young: -37 ± 3, older: -36 ± 3; tyramine, young: -41 ± 2, older: -36 ± 3%ΔCVC_base) and tyrosine (cold, young: -37 ± 4, older: -34 ± 4; tyramine, young: -40 ± 4, older: -45 ± 4%ΔCVC_base) both resolved the age-related decrease in cutaneous vasoconstriction, but BH₄+ tyrosine did not further augment vasoconstriction (cold, young: -38 ± 4, older: -31 ± 3; tyramine, young: -36 ± 3, older: -36 ± 5%ΔCVC_base). These data are consistent with the concept that reduced bioavailability of BH₄ and/or tyrosine may impair noradrenaline synthesis and contribute to the attenuated vasoconstrictor response in aged skin.